Single daily doses of saquinavir achieve HIV-inhibitory concentrations when combined with baby-dose ritonavir

Dual protease inhibitor (PI) therapy has been established either in order to increase plasma concentrations of one PI or to combine synergistic effects of two PI's on viral load. Studies with saquinavir (SQV) and small doses of ritonavir (RTV) as well as experiences from our therapeutic drug monitoring suggest that single daily doses may result in sufficient SQV serum levels throughout an interval of 24 h. A controlled, randomized trial with 20 healthy men was conducted for the comparison of serum levels with 1600 mg SQV (group 1) or 1600 mg SQV/200 mg RTV (group 2). The dosages were selected in order to use RTV as an inhibitor of cytochrome P450 3A4 and SQV as protease inhibitor. The volunteers received single daily doses following a standardized breakfast on 3 consecutive days. Serum samples were analyzed for SQV and RTV employing LC-tandem mass spectrometry. The minimum concentration of saquinavir after 24 hours, the AUC, the maximum concentration and the serum half-lives on day 3 served as target parameters. The minimum SQV concentration amounted to 469.4 ng/ml, when combined with RTV and proved to be significantly higher (p <0.05) than the corresponding concentration with SQV alone (127.3 ng/ml). The SQV maximum concentration was raised approximately 6fold and the AUC 9fold when RTV was coadministered. In combination with 200 mg of RTV the predominant elimination half-life of SQV increased from 2.6 to 6.45 hours. These data prove that under single daily doses of 1600 mg SQV/200 mg RTV HIV-inhibitory concentrations of SQV can be achieved for 24 hours. Due to the high variability of the concentrations, which can be seen with all PI s, we recommend continuous therapeutic drug monitoring of serum trough levels.     

Amprenavir in pre-treated patients: virological and immunological response in a cohort of 45 patients

Treatment failure after preceding protease inhibitors (PI) is often due to resistance mutations. Our objective was to evaluate amprenavir (APV) in pre-treated patients and to correlate it with pre-existing mutations. - Fourty five patients were entered in an open label prospective study (6/99-12/2000). Pre-treatment was 6.2 years +/- 2.4 (2-11.3) and included a mean of 4.13 nucleosides (RTIs) and 2.73 PIs. Genotypic resistance testing was performed prior to the switch. APV dose was 1200 mg/d in combination with ritonavir (RTV) boosting (2 x 100mg) and 2 x 1200 mg/d in 6 patients without RTV. Co-medication was selected based on treatment history and results of genotypic testing. - The median duration of treatment at analysis was 34 weeks. Plasma viral load (VL) average at baseline was 4.6 log subset 10 +/- 08. After 24 weeks the mean VL reduction was 1.4 log subset 10 +/- 1.2 3.86-0.40s). A VL reduction of >1.5 log subset 10 was found in 16/45 patients (36%), 21/45 (47%) patients achieved a VL <400 cp/ml, and 12/45 (27%) a VL < 50 cp/ml. CD4 cells increased from a mean baseline of 208/microl +/- 185 to 318/microl +/- 253. Fourty percent (18/45) of patients had a CD4 gain of more than 100 cells/microl. Genotypic resistance determination showed PI mutations in 87% of patients tested. The average number of mutated codons was 4.54. Three of 4 patients with I84V mutation did not achieve an undetectable VL. - Our findings demonstrate that APV and APV/RTV plus two additional antiretrovirals has a good virological and immunological success rate in pre-treated patients. Presence of more than two APV resistance mutations was associated with treatment failure.     

缓释烟酸及其与阿托伐他汀合用的调脂疗效与安全性

目的 观察烟酸缓释片单用和与阿托伐他汀合用对冠心病及其等危症患者的调脂疗效及安全性。方法 110例血清总胆固醇（TC）≥3．5mmoL／L的冠心病及其等危症患者分为3组：（1）烟酸缓释片组（n=38）,给予烟酸缓释片500mg／d,4周后加量至1000mg／d;（2）阿托伐他汀组（n=38）,给予阿托伐他汀10mg／d;（3）联合治疗组（n=34）,给予阿托伐他汀10mg／d和烟酸缓释片500mg／d,4周后烟酸缓释片加量至1000mg／d。3组患者均干预8周,分别在干预前、干预4周和8周后测定血脂水平并评估不良反应。结果 （1）烟酸缓释片组干预8周后,甘油三酯（TG）降低30％,高密度脂蛋白-胆固醇（HDL-C）升高16％（均P〈0．05）;阿托伐他汀组干预8周后TC、低密度脂蛋白．胆固醇（LDL-C）、TG分别降低19％、26％和17％（均P〈0．05）;联合治疗组干预8周后TC、LDL-C和TG分别降低28％、38％和39％,HDL-C升高23％（均P〈0．05）,其TC和LDL-C的降低明显优于单药治疗组（均P〈0．05）。（2）联合治疗组的LDL-C达标率为73．5％,明显高于单药治疗组（均P〈0．05）。（3）烟酸缓释片组的不良反应以潮红（15．8％）和消化道症状（23．7％）较常见,联合治疗组不良反应未见增加,各组均未见严重的不良反应。结论 烟酸缓释片有良好的调脂作用,尤以降低TG和升高HDL-C效果明显。烟酸缓释片与他汀类药物联合使用有助于血脂谱的全面改善,并具有良好的安全性和耐受性。     

不同剂量阿托伐他汀对不稳定心绞痛患者血脂及血清淀粉样蛋白A、C反应蛋白的影响

目的 观察不同剂量阿托伐他汀对不稳定心绞痛患者血脂及血清淀粉样蛋白A、C反应蛋白的影响、调脂作用和安全性.方法 选取我院2009年5月至2010年10月在心内科住院并诊断为不稳定心绞痛的患者78例,随机分为20 mg组40例:常规治疗加阿托伐他汀20 mg; 40 mg组38例:常规治疗加阿托伐他汀40 mg.另选取我院健康体检者13名作为对照组.分别检测患者治疗前和治疗14d后以及对照组血脂、血清淀粉样蛋白A和C反应蛋白水平.对患者进行冠脉造影,记录病变支数.结果 治疗前不稳定心绞痛患者TC、LDL-C、血清淀粉样蛋白A和C反应蛋白水平高于健康对照组(P＜0.05).患者冠脉病变以双支病变为多见,不同病变支数患者的血清淀粉样蛋白A和C反应蛋白水平差异无统计学意义(P＞0.05).两组患者治疗后血脂水平均有下降.40mg组治疗后血清淀粉样蛋白A和C反应蛋白含量分别为(1 752±262)ng/ml、(3.87±0.33)mg/ml,明显低于20 mg组的(2 598±286)ng/ml、(4.95±0.48)mg/ml(P＜0.05).结论 不稳定心绞痛患者血清淀粉样蛋白A、C反应蛋白水平明显上升,应用阿托伐他汀可以显著降低血清淀粉样蛋白A、C反应蛋白水平,而与TC、LDL-C的降低无相关性.血清淀粉样蛋白A、C反应蛋白降低程度可能与辛伐他汀剂量有关,40 mg降脂治疗可能具有更大的治疗意义.     

腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症的临床研究

目的　评估腺苷蛋氨酸 (SAMe)联合熊去氧胆酸 (UDCA)治疗妊娠期肝内胆汁淤积症 (ICP)的效果。方法　选择 6 3例ICP患者 ,随机分成 3组 ,SAMe联合UDCA组 (A组 ,2 1例 )采用SAMe 10 0 0mg加 5 %葡萄糖液 5 0 0ml静滴 ,1次 /d ,UDCA 10 0mg/次 ,3次 /d ,10天为 1个疗程。SAMe对照组 (B组 ) :用SAMe 10 0 0mg加 5 %葡萄糖液 5 0 0ml静滴 ,1次 /d,10天为 1个疗程。UDCA对照组 (C组 ) :单用UDCA 10 0mg/次 ,3次 /d ,10天为 1个疗程 ,观察 3组的疗效。结果　治疗后 3组患者瘙痒症状的评分间差别有显著性意义 (P <0 0 1)。治疗后 3组患者血清TBA、AST、ALT、TBil、DBil含量间的差别均有显著性意义 (P <0 0 1)。妊娠结局 :A组新生儿早产率 ,羊水污染率 ,新生儿窒息率与B组、C组间差别均有显著性意义。 3组患者新生儿体重间的差别也有显著性意义 (P <0 0 1)。结论　SAMe联合UDCA是治疗ICP的安全有效的方法 ,可改善妊娠预后。     

The Effect of calmodulin antagonist berbaminederivative- EBB on hepatoma in vi tro and in vivo

Objective To evaluate the anti- hepatoma effect of Calmodulin antagonist 0- 4- ethoxyl- butyl- Berbamine (EBB), one of the berbamine derivatives. Methods Monotetrazolium (MTT) method was used to analysize the effect of EBB on the proliferation and growth inhibition effect Of a hepatoma cell line in vitro.A mouse hepatoma model was induced by injection of hepatoma ells (H22) in the abdominal cavity.The effect of EBB on survival at different concentrations as well as in combination with 5- FU were investigated in vivo.Flow cytometry analysis, dot blot hybridization, western blot, immunochemistry, enzyme- linked lectin assay (ELISA), trifluoperazine (TFP) and electron microscopic observation were used to study the effect of EBB on cell cycle process, P53 mRNA and protein levels, calmodulin content and ultrastractural changes of hepatome cells. Results EBB exerts a very strong inhibitory effect on human hepatoma cell line 7402 and mouse hepatoma cell line H22 in vitro.The IC(50) value of EBB for the two cell lines are 3.312 μg/ml and 1.167 μg/ml, respectively.The sensitivity of H22 cells to 5- FU can be markedly enhanced: The IC(50) dosage of 5- Fu can be decreased from 0.75 μg/ml down to 0.15 μg/ml, when jointly administered with nontoxic dosages of EBB (IC10 ).In vivo, EBB can prolong the lifespan of mice with ascites H22 to more than three months.64% of mice survived, while all animals in the control group died by the 18th day.When EBB (5 mg·kg (- 1) ·d( - 1) ) is jointly used with 5- FU (25 mg·ml - 1 ·d[ - 1 ), 73% of mice with ascites H22 survived, much higher than 27% in the 5- FU treated group.EBB can enhance the anti- hepatoma ability of 5- Fu treatment.EBB mechanism against hepatoma: P53 expression in the EBB treated group is substantially higher than that in the control group.EBB increased the translation of P53.As a calmodulin antagonist, EBB decreases amount of the CaM in hepatoma cells and blocked the hepatoma cell proliferation cycle at the G 2M phase.Before the G 0/G 1 phase, a diploid peak and apoptic cells in the treated groups were observed. Conclusions The CaM antagonist, EBB, has a strong anti- hepatoma effect and enhances the effect of 5- FU, induces hepatoma cell to apotopsis, promotes the P53 protein expression and decreases the amount of CaM in the cytoplasm.All these results demonstrate that EBB is a new and potentially useful drug against hepatoma and should be researched further.     

干扰素诱导人肝细胞癌胸苷磷酸化酶表达和拮抗血管生成的实验研究

目的研究干扰素α(IFNα)对人肝细胞癌胸苷磷酸化酶(TP)表达水平及血管生成能力的影响。方法在体内外用一定剂量的IFNα处理人肝癌细胞SMMC7721,用RTPCR和ELISA方法分别检测细胞TPmRNA和蛋白表达水平,Boyden小室法检测诱导内皮细胞移动的能力,免疫组化法检测SMMC7721裸鼠皮下移植瘤组织中微血管密度(MVD)。结果IFNα上调SMMC7721细胞TPmRNA表达水平,呈现剂量依赖性。与未处理组相比,浓度为5000、10000U/ml的IFNα处理的细胞TPmRNA表达水平显著升高(P<0.05),但诱导内皮细胞移动的能力差异无统计学意义。随着IFNα剂量的增加,裸鼠皮下移植瘤组织中TP蛋白表达水平逐渐增加,而MVD数目先增加后下降。IFNα不同剂量时(9.0×106、1.5×107U·kg-1·d-1),肿瘤组织中TP蛋白表达水平显著高于(48ng/mg±24ng/mg)未处理组(60ng/mg±6ng/mg,P<0.01);MVD数目分别为6.0±1.8,4.0±1.5,P<0.05)。与未处理组相比IFNα(1.5×107U·kg-1·d-1)组肿瘤重量明显下降(P<0.05)。结论一定剂量的IFNα既能上调肝细胞癌TP表达水平,又能抵消TP表达上调后促进血管生成能力的增强。     

阿德福韦酯和替比夫定单药治疗慢性乙型肝炎对肾脏功能影响的比较

目的比较阿德福韦酯(ADV)及替比夫定(L-DT)单药治疗慢性乙型肝炎和肝硬化患者对肾脏功能的影响。方法回顾性分析接受ADV(n=46)及L-DT(n=55)单药治疗的101名慢性乙型肝炎和肝硬化患者,比较治疗52周的血清肌酐(CR)、估算肾小球滤过率(eGFR)较基线的变化情况及eGFR≥90 ml.min-.11.73 m-2患者的比例。结果 52周时,ADV和L-DT组患者CR较基线变化平均值分别为+0.05和-0.12 mg/dl(ADV vs L-DT,P=0.000),未观察到CR较基线升高>0.50 mg/dl患者;eGFR较基线变化中位数分别为-4.09和+18.32 ml.min-.11.73 m-(2ADV vs L-DT,P=0.000);基线肾功能轻度受损(eGFR<90 ml.min-.11.73 m-2)的患者中,ADV组有37.50%(3/8)在52周时上升至大于90 ml.min-1.1.73 m-2,L-DT组有92.31%(12/13)上升至大于90 ml.min-.11.73 m-2;ADV组eGFR≥90 ml.min-.11.73 m-2患者比例由基线的82.61%降至52周的78.26%,而L-DT组eGFR≥90 ml.min-1.1.73 m-2患者比例由基线的76.36%升至52周的94.55%;两组不同eGFR水平患者的构成比在基线时无统计学差异(P=0.443),52周时有统计学差异(P=0.015)。结论 L-DT抗病毒治疗对于肾脏功能具有一定的保护作用,但具体机制不明,需要进一步研究。     

Effect of short-term high-dose atorvastatin on systemic inflammatory response and myocardial ischemic injury in patients with unstable angina pectoris undergoing percutaneous coronary intervention

Background Percutaneous coronary intervention （PCI） could develop periprocedural myocardial infarction and inflammatory response and statins can modify inflammatory responses property.The aim of this study was to evaluate whether short-term high-dose atorvastatin therapy can reduce inflammatory response and myocardial ischemic injury elicited by PCI.Methods From March 2012 to May 2014,one hundred and sixty-five statin-naive patients with unstable angina referred for PCI at Department of Cardiology of the 306th Hospital,were enrolled and randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group （HD group,n=56） or 20 mg/d as normal dose group （ND group,n=57） or an additional single high loading dose （80 mg） followed 6-day atorvastatin 20 mg/d as loading dose group （LD group,n=52）.Plasma C-reactive protein （CRP） and interleukin-6 （IL-6） levels were determined before intervention and at 5 minutes,24 hours,48 hours,72 hours,and 7 days after intervention.Creatine kinase-myocardial isoenzyme （CK-MB） and cardiac troponin I （cTnl） were measured at baseline and then 24 hours following PCI.Results Plasma CRP and IL-6 levels increased from baseline after PCI in all groups.CRP reached a maximum at 48 hours and IL-6 level reached a maximum at 24 hours after PCI.Plasma CRP levels at 24 hours after PCI were significantly lower in the HD group （（9.14±3.02） mg/L） than in the LD group （（11.06±3.06） mg/L） and ND group （（12.36±3.08） mg/L,P ＜0.01）; this effect persisted for 72 hours.IL-6 levels at 24 hours and 48 hours showed a statistically significant decrease in the HD group （（16.19±5.39） ng/L and （14.26±4.12） ng/L,respectively）） than in the LD group （（19.26±6.34） ng/L and （16.03±4.08） ng/L,respectively,both P ＜0.05） and ND group （（22.24±6.98） ng/L and （17.24±4.84） ng/L,respectively）.IL-6 levels at 72 hours and 7 days showed no statistically significant difference among the study groups.Although PCI cau     

Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: a prospective study from China

Background  Early detection and diagnosis is urgent for the sake of effective treatment strategy for lung cancer. However, a convenient, economical and relatively precise method is not available. We here report a prospective study to find the possible value of the combined use of four popular tumor markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung.

Methods  Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumor group according to post-operative histological examinations. Serum levels of four tumor markers including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), Cyfra 21-1 and neuron specific enolase (NSE) were assayed for each patient. Receiver operating characteristic (ROC) curves were constructed for each tumor marker. The power of lung cancer diagnosis of each tumor marker, as well as a combination of them were analyzed and compared.

Results  The serum levels (median, range) of SCC, CEA, Cyfra 21-1 and NSE were 0.44 (0.01–35.70) ng/ml, 2.49 (0.30–26.78) ng/ml, 2.30 (0.82–73.33) ng/ml and 10.54 (0.10–56.41) ng/ml respectively in lung cancer group, and were 0.32 (0.01–0.90) ng/ml, 1.60 (0.20–8.93) ng/ml, 1.41 (0.72–4.82) ng/ml and 9.36 (6.56–24.24) ng/ml respectively in the benign pulmonary tumor group. The difference in each tumor marker between the two groups was significant (P <0.05). The ROCs of SCC, CEA, Cyfra 21-1 and NSE were 0.702 (95% CI, 0.654–0.751), 0.611 (95% CI, 0.563–0.659), 0.650 (95% CI, 0.601–0.700) and 0.598 (95% CI, 0.542–0.654) respectively, indicating very low power of these four tumor markers. When a combination of SCC, CEA, Cyfra 21-1 and NSE were employed, the diagnosis power was strengthened.

Conclusion  SCC, CEA, Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung, especially when they were assayed together for one patient.

     

老年卒中后抑郁患者血浆瘦素及胰岛素样生长因子-1水平的相关性研究

目的 探讨老年卒中后抑郁患者血清瘦素(leptin)、胰岛素样生长因子-1(IGF-1)、脑源性神经营养因子(BDNF)及炎性标志物水平变化及意义.方法 以老年缺血性卒中患者为研究对象,采用汉密尔顿抑郁量表筛选符合条件的卒中后抑郁患者46例,选择不伴抑郁的老年卒中患者50例为对照组.于住院第3周,应用酶联免疫吸附法检测患者血清leptin、IGF-1、BDNF以及炎性标志物超敏C反应蛋白(hsCRP)、细胞间黏附分子(ICAM-1)浓度.结果 (1)卒中后抑郁组血清leptin和IGF-1浓度[分别为(57.4±14.32)ng/ml、(120.86±28.66)ng/ml]较对照组[分别为(17.53±11.62)ng/ml、(66.5±17.51)ng/ml]明显增高,差异有显著性意义(P＜0.01).(2)卒中后抑郁组血清hs-CRP[(2.3±0.42)mg/dl]、ICMA-1[(182.6±50.27)ng/ml]、BDNF[(25.8±8.35)ng/ml]与对照组hs-CRP[(2.2±0.28)mg/dl]、ICMA-1[(178.7±51.14 ng/ml]、BDNF[(24.2±7.48)ng/ml]比较差异无显著性(P＞0.05).(3)血浆leptin和IGF-1与HAMD显著相关(相关系数分别为:r=0.724,P＜0.01;r=0.641,P＜0.01).结论 Leptin和IGF-1与老年卒中后抑郁关系密切,可能是老年卒中后抑郁的血清标志物.     

核苷(酸)单药与联合治疗失代偿期乙型肝炎肝硬化疗效的比较

目的 比较核苷(酸)单药与联合治疗对失代偿期乙型肝炎肝硬化患者的疗效.方法 回顾性分析130例核苷(酸)单药或联合治疗失代偿期乙型肝炎肝硬化患者的临床资料.单药组111例,其中恩替卡韦组(ETV)25例,阿德福韦酯组(ADV)45例,拉米夫定组(LAM)41例;联合组[替比夫定(LDT)+ADV]19例.于治疗后4、1...     

Safety and efficacy after switch to a saquinavir-containing antiretroviral regimen in protease inhibitor pretreated HIV-positive patients

Objective

The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naïve patients.

Methods

Multicenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48.

Results

A total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels < 50 copies/mL at week 48 was 60.3% (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm³ from baseline (p < 0.01) and 60.3% of patients achieved HIV-1 RNA < 50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride < 200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR 1024; 0) for baseline triglyceride > 750 mg/dL (p < 0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC < 200 mg/dL (p < 0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC > 300 mg/dL (p < 0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects.

Conclusions

These data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naïve patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.     

普伐他汀联合杏丁注射液治疗不稳定型心绞痛疗效观察

目的通过观察不同剂量普伐他汀联合杏丁注射液早期应用对不稳定型心绞痛患者血脂及C反应蛋白（C-reactive protein,CRP）的影响,探讨其对不稳定型心绞痛的疗效。方法选择入院后诊断为不稳定型心绞痛的患者118例,随机分为四组,①A组：常规治疗加普伐他汀20mg组30例;②B组：常规治疗加普伐他汀20mg及杏丁组29例;③C组：常规治疗加普伐他汀40mg组28例;④D组：常规治疗加普伐他汀40mg及杏丁组31例。分别在确诊后、治疗后3周检查血脂和CRP的水平。结果与治疗前相比,不稳定型心绞痛患者在分别接受上述治疗后,总胆固醇（Total choles-terol,TC）、低密度脂蛋白（Low-density lipoprotein-C,LDL-C）、CRP水平均有不同程度的降低（P〈0.05）。其中与A组相比,其余三组的血脂、CRP水平均有不同程度的降低（P〈0.05）,D组的降低水平更为明显（P〈0.01）;加用杏丁注射液治疗后,高密度脂蛋白（High-density lipoprotein,HDL）水平有所升高,在D组升高尤为明显（P〈0.05）。结论不同剂量的普伐他汀均可通过降低血脂及CRP水平来缓解不稳定型心绞痛的症状,达到治疗不稳定型心绞痛的作用,加用杏丁注射液后,其作用更为明显。     

氨氯地平及阿折地平对高血压病患者血浆炎性介质hs-CRP和TIMP-1的影响

目的探讨长效二氢吡啶类（DHPS）降压药物氨氯地平、阿折地平对高血压病患者血浆炎性介质超敏C反应蛋白（hs-CRP）、1-型组织基质金属蛋白酶抑制物（TIMP-1）浓度的影响。方法将55例高血压病患者随机双盲分为氨氯地平组（28例）和阿折地平组（27例）,2组经过2周的药物洗脱期后,分别给予8周的氨氯地平（5～10mg/d）或阿折地平（8～16mg/d）治疗,在治疗前后对血压情况及hs-CRP、TIMP-1进行监测。结果2组患者治疗后收缩压和舒张压均显著下降,血压达标率分别为67.9%和70.4%。氨氯地平组hs-CRP治疗前后分别为（4.48±4.64）mg/L、（1.49±1.62）mg/L,阿折地平组分别为（3.44±1.58）mg/L、（1.19±0.95）mg/L;氨氯地平组TIMP-1治疗前后分别为（78.31±46.21）ng/ml、（55.12±31.17）ng/ml,阿折地平组分别为（73.89±27.69）ng/ml、（45.69±16.87）ng/ml,均显著下降（P均〈0.05）。结论氨氯地平和阿折地平对高血压病患者在有效降压的同时,均能降低血浆中炎性介质hs-CRP、TIMP-1的含量,可能在一定程度上降低高血压靶器官的损伤。     

COPD急性发作期患者外周血IL-35、hs-CRP检测及临床意义

目的 观察慢性阻塞性肺疾病急性发作期(acute exacerbation of chronic obstructive pulmonary disease, AECOPD)患者外周血IL-35、hs-CRP水平,并探讨其临床意义。 方法 80例COPD患者分为急性发作期组(A组,n=49)和稳定期组(B组,n=31),同期健康体检者25名为对照者(C组,n=25)。ELISA法检测3组外周血清IL-35表达;检测3组外周血清hs-CRP。 结果COPD患者B组、A组外周血清IL-35表达水平分别为(4.171±1.339)ng/ml、(3.480±1.790)ng/ml,与对照组[(5.194±1.595)ng/ml]相比,差异有统计学意义(P<0.05);B组与A组相比,差异无统计学意义(P>0.05)。A组患者血清hs-CRP水平[(61.143±30.024)mg/L]明显高于B组和C组[(12.161±4.495mg/L、(1.075±0.855)mg/L],差异有统计学意义(P<0.05)。A组外周血清IL-35与hs-CRP呈负相关性(r=-0.349,P=0.014),B组无负相关(r=-0.237,P=0.199)。 结论 AECOPD患者外周血清IL-35低表达及hs-CRP高表达,两者联合检测可作为临床诊断AECOPD的辅助指标。     

胃蛋白酶原1 对晚期胃癌临床预后的预测价值

目的 探讨胃蛋白酶原1（PG1）对接受不同化疗联合靶向治疗方案的晚期胃癌（AGC）患者 临床预后的预测价值。方法 选取2011 年2 月—2013 年4 月于河南省南阳市中心医院就诊的AGC 患者109 例，根据治疗方案分为FLO 组和SOX 组，比较两组患者3、5 年生存率，以受试者工作特征（ROC）曲线 分析PG1 对临床预后的预测价值，并采用单因素和多因素回归分析影响AGC 生存率的危险因素。结果 A 组与B 组的3 和5 年生存率比较，差异无统计学意义（P >0.05）。PG1 预测FLO 组、SOX 组患者5 年生存 率的ROC 曲线下面积分别为0.869 和0.717，差异有统计学意义（P <0.05），FLO 组、SOX 组诊断折点分别 为54.43 和50.39 ng/ml ；FLO 组敏感性、特异性、阳性预测值、阴性预测值分别为79.3%、85.4%，80.9%、 86.1%，SOX 组分别为78.3%、82.9%，83.0%、80.1%，PG1 对FLO 组的预测价值高于SOX 组。单因素分析 结果表明，3 和5 年随访结束时死亡患者组织学低分化和PG1 ≤ 52.26 ng/ml 比例大于生存患者（P <0.05）。 多因素Logistic 回归分析结果表明，BMI>24 kg/m2 [Ol ^ R=1.103，（95% CI ：1.038，1.242），P =0.013]、组织 学低分化[Ol ^ R=1.107，（95% CI ：1.025，1.305），P =0.004]、脂肪肝[Ol ^ R=1.034，（95% CI ：1.006，1.323）， P =0.011]、PG1 ≤ 52.26 ng/ml [Ol ^ R=1.216，（95% CI：1.013，1.407），P =0.024] 是影响AGC 生存率的危险因素。 结论 PG1 对AGC 临床预后具有一定的预测价值，其中对FLO 治疗方案的预测意义更大。     

Digoxin toxicity: clinical and laboratory assessment

A prospective study to correlate clinical digoxin toxicity with serum digoxin levels was carried out in 67 patients of whom 24 were clinically toxic and 43 were asymptomatic. The patients were clinically diagnosed to be toxic based on typical cardiac arrhythmias (n = 11) or non-cardiac symptoms (n = 13). Blood samples were collected at least six hours after the last digoxin dose and the sera assayed for digoxin using a radioimmunoassay method. The mean serum digoxin level in the toxic group (x1 = 2.09 +/- 1.28 ng/ml) was significantly higher than in the non-toxic group (x2 = 1.20 +/- 0.75 ng/ml), p less than 0.01. All the non-toxic patients had serum digoxin levels below 3 ng/ml. However, there was a considerable overlap of serum digoxin levels between the two groups of patients. Serum level cannot be the sole criterion in diagnosing digoxin toxicity. Nevertheless, raised serum digoxin levels especially above 3 ng/ml, in the presence of suggestive clinical features is strongly suggestive of toxicity.     

不同浓度瑞芬太尼对地氟醚最低肺泡有效浓度的影响

目的:观察不同浓度瑞芬太尼对地氟醚最低肺泡有效浓度(MAC)的影响。方法:以脑电双频谱指数(BIS)=50作为指标来确定地氟醚的ED50值(MACBIS50),将80例患者鼓室成形术随机分为A、B、C、D、E5组(每组16例),接受瑞芬太尼静脉输注靶控血浆浓度分别为0,2,4,6,8ng/ml。患者术前用阿托品0.01mg/kg肌肉注射,全麻诱导采用咪达唑仑0.02mg/kg,异丙酚2mg/kg,维库溴铵0.1～0.2mg/kg。诱导插管后按靶控血浆浓度泵控输注瑞芬太尼并吸入地氟醚,待地氟醚呼气末浓度(ET%)达到预定值并稳定10min后,手术切皮并记录相应的BIS值。采用上下波动法分别计算各组的地氟醚MACBIS50,BIS值和ET%进行直线回归分析。结果:5组患者地氟醚MACBIS50值分别为7.18%,6.31%,4.18%,2.86%和2.19%。与A组比较,其余4组的MACBIS50显著降低(P<0.05)。各组BIS和ET%直线相关。结论:瑞芬太尼复合地氟醚麻醉可显著降低地氟醚MAC,并呈剂量依赖性降低,瑞芬太尼超过8ng/ml时,下降速度趋缓,逐渐出现封顶效应。并保持BIS值和呼气末浓度的直线相关性。     

Prevalence of dyslipidemia and dysglycaemia in HIV infected patients

BACKGROUND: Highly active antiretroviral therapy (HAART) has dramatically reduced AIDS morbidity and mortality, however long-term metabolic consequences including dysglycaemia and dyslipidemia have raised concern regarding accelerated cardiovascular disease risk. OBJECTIVE: To determine the period prevalence of dyslipidemia and dysglycaemia in HIV-infected patients. DESIGN: Cross-sectional comparative group study. SETTING: Kenyatta National Hospital, a tertiary HIV dedicated out-patient facility. SUBJECTS: Consecutive HIV- positive adult patients. MAIN OUTCOME MEASURES: Dyslipidemia: presence of raised total or LDL cholesterol or low HDL cholesterol, or raised triglycerides. Dysglycaemia: presence of impaired fasting glucose or impaired glucose tolerance, or diabetes mellitus. Results: Between January and April 2006, out of 342 screened patients, 295 were recruited and 58% were females. One hundred and thirty four (45%) were on HAART, 82% of whom were on stavudine, lamivudine and either nevirapine or efavirenz. Overall prevalence of dyslipidemiawas 63.1% and dysglycaemia was 20.7%. High total cholesterol occurred in 39.2% of HAART and 10.0% HAART naive patients (p<0.0001, OR 5.18, CI 3.11-10.86), whereas high LDL cholesterol occurred in 40.8% and in 11.2% respectively (p<0.0001, OR 5.43, CI 2.973-9.917). HDL levels were low in 14.6% and 51.3% among HAART and HAART naive patients, respectively, (p<0.0001, OR 0.16, CI 0.091-0.29) while high triglycerides occurred in 25.6% and 22.5% respectively (p=0.541 OR 1.184 CI 0.688-2.037). Among patients on HAART compared to HAART naive patients, diabetes was found in 1.5% against 1.2% (p=0.85), impaired fasting in 2.2% against 0.6% (p=0.30) and impaired glucose tolerance in 16.4% against 21.1% (p=0.22), respectively. CONCLUSIONS: HIV- infected patients demonstrated a high prevalence of dyslipidemia. HAART use was associated with high levels of total, and LDL cholesterol and high triglyceride levels, an established athrogenic lipid profile. However, HAART was not associated with low HDL cholesterol and had no significant effect on dysglycaemia.